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Gamma-irradiation enhances RECK protein levels in Panc-1 pancreatic cancer cells

Authors
Kim, Na YoungLee, Jung EunChang, Hyeu JinLim, Chae SeungNam, Deok HwaMin, Bon HongPark, Gil HongOh, Jun Seo
Issue Date
29-2월-2008
Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
Keywords
extracellular matrix; radiation; RECK; TGF-beta; TIMP
Citation
MOLECULES AND CELLS, v.25, no.1, pp.105 - 111
Indexed
SCIE
SCOPUS
KCI
Journal Title
MOLECULES AND CELLS
Volume
25
Number
1
Start Page
105
End Page
111
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/124055
ISSN
1016-8478
Abstract
Radiotherapy is an important treatment for many malignant tumors, but there are recent reports that radiation may increase the malignancy of cancer cells by stimulating expression of type IV collagenases. In this study, we examined changes in matrix metalloproteinase (MMP) inhibitors, such as the tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and RECK, in response to irradiation in Panc-1 pancreatic cancer cells. Irradiation increased RECK protein levels but not mRNA levels, whereas no significant changes were found in TIMP-1 and TIMP-2. The enhanced RECK protein levels were associated with an increase in MMP inhibitory activity. However, irradiation slightly but reproducibly increased the invasiveness of the Panc-1 cells. Like irradiation, treatment of Panc-1 cells with transforming growth factor (TGF)-beta 1 led to a 2-fold increase in RECK protein levels. Transient transfection with Smad3 also increased RECK protein levels, but transfection with Smad7 markedly reduced them. Stable expression of Smad7 and treatment with SB431542, an inhibitor of TGF-beta receptor I kinase, abolished TGF-beta 1- and radiation-mediated effects on RECK. Furthermore, irradiation increased levels of phosphorylated Smad3. We conclude that radiation post-transciption ally enhances RECK protein levels in Panc-1 cells, at least in part, via TGF-beta signaling, and that irradiation increases Panc-1 invasiveness via a mechanism that may not be linked to MMP-2 activity.
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